It is also possible to use genome-wide association data to estimate the total amount of phenotypic variation that can be explained by common genetic variation (101). However, it is not possible to extrapolate from the total amount of heritability accounted for in toto to the variance explained by any individual undiscovered locus, and therefore difficult to use these estimates to predict the likely number of new loci or variants that would be identified by future GWA studies. Bayesian approaches have been used to infer the effect size (and frequency) distribution of undiscovered variants (89), although predictions from this method have not yet been compared to results from subsequent studies. Of course, if the total variance explained already approaches the estimated total heritability, further studies are unlikely to be useful. The variance explained in the usual additive models may also underestimate the total heritability accounted for, both because of multiple variants within each locus (20, 26, 54, 84, 102), and also in theory because of complex interactions that could lead to underestimation of the variance explained (104).
